Cited by 812Autophagy in Disease and TherapyParkinson's Disease Mechanisms and TreatmentsAmyotrophic Lateral Sclerosis Research

Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation

Open access
Wong, Yvette C., Holzbaur, Erika L. F.·2014·Proceedings of the National Academy of Sciences

Abstract

Significance: In mitophagy, damaged mitochondria recruit parkin to ubiquitinate proteins on the outer mitochondrial membrane, targeting mitochondria for autophagosome engulfment and degradation. However, the proteins involved in mediating autophagosome formation to degrade damaged and ubiquitinated mitochondria remain unknown. We used live cell imaging to demonstrate that optineurin is actively recruited to parkin-labeled ubiquitinated mitochondria and is stabilized by its ubiquitin binding domain. Optineurin binds the autophagosome protein LC3 (microtubule-associated protein light chain 3), and this binding recruits autophagosome assembly around damaged mitochondria. We find that the E478G optineurin mutation, causative for the neurodegenerative disease amyotrophic lateral sclerosis, disrupts autophagosome recruitment. As mutations in parkin are linked to Parkinson’s disease, this study indicates that defects in a single mitochondrial degradation pathway lead to neurodegenerative diseases with distinct pathologies.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1073/pnas.1405752111

Cites

47 of 47 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Upon mitochondrial damage, OPTN translocates to the surface of mitochondria, an interaction stabilized via TBK1-mediated phosphorylation, facilitating engulfment of mitochondria into phagophores.

    “Upon mitochondrial damage, OPTN translocates to the surface of mitochondria, an interaction that is stabilized via TBK1-mediated phosphorylation, facilitating the engulfment of mitochondria into phagophores [256].”
  • Mitophagy can also occur through Parkin-independent pathways.

    “Mitophagy can also occur through Parkin-independent pathways.”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Wong, Y. C., & Holzbaur, E. L. F.
Affiliations
University of Pennsylvania (US)
Venue
Proceedings of the National Academy of Sciences
Published
2014-10-07
Volume
111
Issue
42
Pages
E4439-48
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2051362437
Cited by
812
References
47
Citations by year
2026: 34 · 2025: 62 · 2024: 58 · 2023: 68 · 2022: 68 · 2021: 94 · 2020: 88 · 2019: 80 · 2018: 64 · 2017: 61 · 2016: 71 · 2015: 60 · 2014: 4
FWCI
49.50
Type
journal article
Language
en
Open access
Locations
  • Proceedings of the National Academy of Sciences (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Neurological Disorders and Stroke (R37NS060698, R01NS060698)
Topics
  • Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
  • Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
  • Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
Keywords
optineurin, mitophagy, Parkin, autophagy receptors, amyotrophic lateral sclerosis, E3 ubiquitin ligase, LC3, autophagosome formation, p62, mitochondrial dysfunction, ubiquitin-binding domain, reactive oxygen species, mitochondrial depolarization, neurodegenerative diseases
MeSH terms
Sequestosome-1 Protein, Amyotrophic Lateral Sclerosis, Autophagy, HeLa Cells, Humans, Microtubule-Associated Proteins, Microtubules, Mitochondria, Mutation, Parkinson Disease, Phagosomes, Protein Binding, Protein Structure, Tertiary, Microscopy, Confocal, Cell Cycle Proteins, Neurodegenerative Diseases, Membrane Transport Proteins, RNA, Small Interfering, Transcription Factor TFIIIA, Ubiquitin-Protein Ligases, Adaptor Proteins, Signal Transducing, Green Fluorescent Proteins, Mitochondrial Membranes, Mitophagy

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review